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Heart failure-related cardiogenic shock (HF-CS) remains an understudied distinct clinical entity.The authors sought to profile a large cohort of patients with HF-CS focused on practical application of the Society of Cardiovascular AngiographyCardiovascular Interventions (SCAI) staging system to define baseline and maximal shock severity, in-hospital management with acute mechanical circulatory support (AMCS), and clinical outcomes.The Cardiogenic Shock Working Group registry includes patients with CS, regardless of etiology, from 17 clinical sites enrolled between 2016 and 2020. Patients with HF-CS (non-acute myocardial infarction) were analyzed and classified based on clinical presentation, outcomes at discharge, and shock severity defined by SCAI stages.A total of 1,767 patients with HF-CS were included, of whom 349 (19.8%) had de novo HF-CS (DNHF-CS). Patients were more likely to present in SCAI stage C or D and achieve maximum SCAI stage D. Patients with DNHF-CS were more likely to experience in-hospital death and in- and out-of-hospital cardiac arrest, and they escalated more rapidly to a maximum achieved SCAI stage, compared to patients with acute-on-chronic HF-CS. In-hospital cardiac arrest was associated with greater in-hospital death regardless of clinical presentation (de novo: 63% vs 21%; acute-on-chronic HF-CS: 65% vs 17%; both P 0.001). Forty-five percent of HF-CS patients were exposed to at least 1 AMCS device throughout hospitalization.In a large contemporary HF-CS cohort, we identified a greater incidence of in-hospital death and cardiac arrest as well as a more rapid escalation to maximum SCAI stage severity among DNHF-CS. AMCS use in HF-CS was common, with significant heterogeneity among device types. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).

Cardiac cell surface proteins are drug targets and useful biomarkers for discriminating among cellular phenotypes and disease states. Here we developed an analytical platform, CellSurfer, that enables quantitative cell surface proteome (surfaceome) profiling of cells present in limited quantities, and we apply it to isolated primary human heart cells. We report experimental evidence of surface localization and extracellular domains for 1,144 N-glycoproteins, including cell-type-restricted and region-restricted glycoproteins. We identified a surface protein specific for healthy cardiomyocytes, LSMEM2, and validated an anti-LSMEM2 monoclonal antibody for flow cytometry and imaging. Surfaceome comparisons among pluripotent stem cell derivatives and their primary counterparts highlighted important differences with direct implications for drug screening and disease modeling. Finally, 20% of cell surface proteins, including LSMEM2, were differentially abundant between failing and non-failing cardiomyocytes. These results represent a rich resource to advance development of cell type and organ-specific targets for drug delivery, disease modeling, immunophenotyping and in vivo imaging

Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices.A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio.The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively.The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

BACKGROUND The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS Patients (≥19 years of age) enrolled into STS Intermacs between August 2017 and June 2019 were stratified by device type (continuous flow, centrifugal left ventricular assist device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by 3 statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS Of 4448 patients, 2012 (45.2%) received the CF-HL and 2436 (54.8%) received the CF-FML. One-year survival for the CF-FML was 88% vs 79% for the CF-HL (overall P < .001), with a hazard ratio for mortality of 3.18 for the CF-HL (P < .0001) after risk adjustment. With propensity score matching (n = 1400 each cohort), 1-year survival was 87% for the CF-FML vs 80% for the CF-HL, with a hazard ratio of 3.20 for mortality with the CF-HL (P < .0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving the CF-HL was associated with a hazard ratio of 3.11 (P < .0001). CONCLUSIONS Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of the CF-FML vs CF-HL.

Cardiogenic shock is a state of end-organ hypoperfusion due to primary cardiac dysfunction and portends a poor prognosis. Shock refractory to inotropic and vasopressor support is often an indication for mechanical circulatory support. When mechanical support device complications or malfunction arise, echocardiography offers rapid assessment of device position and function. Repositioning can be done under echocardiographic guidance. Despite the widespread use of percutaneous mechanical circulatory support, there is a dearth of information regarding echocardiography as it pertains to these devices. In this review, we discuss the utility of echocardiography with percutaneous mechanical circulatory support devices.

The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD).Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy.Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure.Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively.Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

Background Understanding the prognostic impact of right ventricular dysfunction (RVD) in cardiogenic shock (CS) is a key step toward rational diagnostic and treatment algorithms and improved outcomes. Using a large multicenter registry, we assessed (1) the association between hemodynamic markers of RVD and in-hospital mortality, (2) the predictive value of invasive hemodynamic assessment incorporating RV evaluation, and (3) the impact of RVD severity on survival in CS. Methods and Results Inpatients with CS owing to acute myocardial infarction (AMI) or heart failure (HF) between 2016 and 2019 were included. RV parameters (right atrial pressure, right atrial/pulmonary capillary wedge pressure [RA/PCWP], pulmonary artery pulsatility index [PAPI], and right ventricular stroke work index [RVSWI]) were assessed between survivors and nonsurvivors, and between etiology and SCAI stage subcohorts. Multivariable logistic regression analysis determined hemodynamic predictors of in-hospital mortality; the resulting models were compared with SCAI staging alone. Nonsurvivors had a significantly higher right atrial pressure and RA/PCWP and lower PAPI and RVSWI than survivors, consistent with more severe RVD. Compared with AMI, patients with HF had a significantly lower RA/PCWP (0.58 vs 0.66, P = .001) and a higher PAPI (2.71 vs 1.78, P Conclusions RVD is associated with poor outcomes in CS, with key differences across etiology and shock severity. Further studies are needed to assess the usefulness of RVD assessment in guiding therapy.

Purpose Sympathetic activation results in a functional distribution of venous blood from the unstressed reservoir to the hemodynamically active stressed compartment. Such redistribution has been hypothesized to contribute importantly to the elevated filling pressures observed in decompensated heart failure and cardiogenic shock (CS). We recently reported a novel computational method to estimate SBV by fitting measured hemodynamic data from patients to outputs from a cardiovascular model. We hypothesized that estimated stressed blood volume (eSBV) may correlate with severity and clinical outcomes in cardiogenic shock. Methods Hemodynamic parameters including eSBV were compared among a subset of patients from the Cardiogenic Shock Working Group (CSWG) registry who had a complete set of hemodynamic data. eSBV was compared across shock etiologies (AMI vs HF-CS), SCAI stage, and between survivors and non-survivors. Results Among 528 CSWG registry patients analyzed, 25.4% had AMI-CS and 61.9% had HF-CS. Mean eSBV was 2423 ± 531 mL/70 kg (normal value ∼1500 mL) and was similar between the AMI-CS and HF-CS subgroups (2421 ± 478 vs 2342 ± 599 mL/70kg, p=0.90). eSBV increased with increasing SCAI stage (B, 2029 ± 540; C, 2305 ± 505; D, 2496 ± 507; E, 2707 ± 420 mL/70 kg, p Conclusion eSBV is a novel integrated index of congestion which correlates with shock severity. eSBV was higher in patients with HF-CS who died while no difference was observed in AMI-CS, suggesting that congestion may play a more significant role in the deterioration of patients with HF-CS.

Background Cardiogenic shock (CS) is critical end-organ hypoperfusion due to reduced cardiac output. Early therapy, such as vasoactive agents or the initiation of mechanical circulatory support (MCS), requires early diagnosis and is associated with better outcomes. A novel ultrasound platform (GE Healthcare, Milwaukee, WI) has semi-automated imaging software (SAIS), which could simplify the point-of-care ultrasound (POCUS) diagnosis of CS. We assessed the feasibility of using POCUS with SAIS in patients in shock, determined the ability of SAIS to identify the subset of patients with CS, and described the process and outcome of care of patients with vs. without CS after presenting to Emergency Department (ED) with hypotension. Methods This prospective case-control study was conducted at an urban ED. Physicians with prior POCUS education received one hour of training with the study device. The qualitative ejection fraction was determined by visual assessment. SAIS measurements of hemodynamics were made with the study device and included left ventricle outflow tract velocity time integral (LVOT VTI), inferior vena cava collapsibility or distensibility indices, and pulmonary B-line assessment. ED patients with a systolic blood pressure ≤ 90 mmHg or need for a vasopressor initiation in the ED were enrolled. The diagnosis of CS was determined by a medical record review. All data were summarized descriptively. Results Twenty-nine cases underwent POCUS, and 87 controls did not. Baseline characteristics, process, and outcome of care were similar between groups. Seventy-nine percent (79%) of cases had a complete POCUS with SAIS. Of these, 55% had reduced LVOT VTI, 38% had IVC collapsibility50%, and 48% of cases had a B-line pattern consistent with pulmonary edema. The mean LVOT VTI for cases with CS was 9.4± 5.4 cm; the mean LVOT VTI for cases without CS was 15.2 ± 6.0 cm. Among patients who did not undergo POCUS, 31 (36%) had a formal echocardiogram, and eight (9%) had a final diagnosis of cardiogenic shock during hospitalization. Conclusion Physicians with one hour of platform-specific training were able to implement POCUS with SAIS among patients who present with shock. POCUS with SAIS may aid in the early recognition of CS.

Objectives: Six months after withdrawal of the HeartWare HVAD System (HVAD; Medtronic) from sale, approximately 4000 patients continue ongoing support with this device. In light of the diminishing experience, this global consensus document summarizes key management recommendations. Methods: International experts with experience in the management of patients with ongoing HVAD support were invited to summarize key aspects of patient and pump management and highlight differences in the current HeartMate 3 (Abbott Laboratories) ventricular assist device. Clinicians from high-implanting HVAD sites reviewed current literature and reported experience to generate a consensus statement. Results: Specific guidelines to assist in the management of ongoing HVAD patients are developed. Key management protocols and helpful techniques developed from experienced clinicians are combined into a short guideline document. As experience with HeartMate 3 increases, key differences in approach to management are highlighted, where appropriate. Conclusions: With decreasing worldwide experience in the ongoing management of HVAD-supported patients, this consensus guideline provides a summary of best practice techniques from international centers. Differences in HeartMate 3 management are highlighted.

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention.

Targeted blood pressure (BP) control is a goal of left ventricular assist device medical management, but the interpretation of values obtained from noninvasive instruments is challenging. In the MOMENTUM 3 Continued Access Protocol, paired BP values in HeartMate 3 (HM3) patients were compared from arterial (A)-line and Doppler opening pressure (DOP) (319 readings in 261 patients) and A-line and automated cuff (281 readings in 247 patients). Pearson (R) correlations between A-line mean arterial (MAP) and systolic blood pressures (SBP) were compared with DOP and cuff measures according to the presence (>1 pulse in 5 seconds) or absence of a palpable radial pulse. There were only moderate correlations between A-line and noninvasive measurements of SBP (DOP R = 0.58; cuff R = 0.47) and MAP (DOP R = 0.48; cuff R = 0.37). DOP accuracy for MAP estimation, defined as the % of readings within ± 10 mmHg of A-line MAP, decreased from 80% to 33% for DOP ≤ 90 vs. >90 mmHg, and precision also diminished (mean absolute difference [MAD] increased from 6.3 ± 5.6 to 16.1 ± 11.4 mmHg). Across pulse pressures, cuff MAPs were within ±10 mmHg of A-line 62.9%-68.8% of measures and MADs were negligible. The presence of a palpable pulse reduced the accuracy and precision of the DOP-MAP estimation but did not impact cuff-MAP accuracy or precision. In summary, DOP may overestimate MAP in some patients on HM3 support. Simultaneous use of DOP and automated cuff and radial pulse may be needed to guide antihypertensive medication titration in outpatients on HM3 support.

Background There are limited data to guide oncology and cardiology decision-making in patients with a left ventricular assist device (LVAD) and concurrent active malignancy. Objectives The goal of this study was to describe cancer treatment approaches, complications, and survival among patients with active cancer on LVAD support in 2 tertiary heart failure and oncology programs. Methods In this retrospective cohort study, LVAD databases were reviewed to identify patients with a cancer diagnosis at the time of or after LVAD implantation. We created a 3:1 matched cohort based on age, sex, etiology of cardiomyopathy, LVAD implant strategy, and INTERMACS profile stratified by site. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival between patients with cancer and non-cancer comparators. Results Among 1,123 patients who underwent LVAD implantation between 2005 and 2019, 22 patients with LVADs with active cancer and 66 matched non-cancer comparators were identified. Median age was 62 years (range 41 to 73 years); 50% of patients with cancer were African-American, and 27% were women. Prostate cancer, followed by renal cell cancer and hematologic malignancies were the most common diagnoses. There was no significant difference in unadjusted Kaplan-Meier median survival estimates from the time of LVAD placement between patients with cancer (3.53 years; 95% confidence interval [CI]: 1.41 to 5.33) and non-cancer comparators (3.03 years; 95% CI: 1.83 to 5.26; log-rank P = 0.99). In Cox proportional hazard models, cancer diagnosis as a time-varying variable was associated with a statistically significant increase in death (hazard ratio: 2.05; 95% CI: 1.03 to 4.12; P = 0.04). Patients with cancer had less gastrointestinal bleeding compared with matched non-cancer comparators (P = 0.016). Other complications were not significantly different. Conclusions Our study provides initial feasibility and safety data and set a framework for multidisciplinary team management of patients with cancer and LVADs., Central Illustration

Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management.The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System.The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Aims Continuous‐flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end‐stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality‐of‐life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost‐effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost‐effectiveness of DT LVADs compared with medical management (MM) in the NHS England. Methods and results We developed a Markov multiple‐state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost‐effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality‐adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. Conclusions The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost‐effective therapy in the NHS England healthcare system under the end‐of‐life willingness‐to‐pay threshold of £50 000/QALY, which applies for VAD patients.

Aims Optimal blood pressure (BP) control is imperative to reduce complications, especially strokes, in continuous flow ventricular assist device (VAD) patients. Doppler BP has been shown to be an accurate and reliable non‐invasive BP measurement method in HeartMate II and HVAD patients. We examined whether Doppler BP is also accurate in patients with the HeartMate 3 VAD. Methods and results In a prospective, longitudinal cohort of HeartMate 3 patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Correlation and agreement between Doppler opening pressure and arterial line mean arterial pressure (MAP) versus systolic blood pressure (SBP) were analysed, as well as the effect of pulse pressure on the accuracy of Doppler opening pressure. A total of 589 pairs of simultaneous Doppler opening pressure and arterial line pressure readings were obtained in 43 patients. Doppler opening pressure had good correlation with intra‐arterial MAP (r = 0.754) and more closely approximated MAP than SBP (mean error 2.0 vs. −8.6 mmHg). Pulse pressure did not have a clinically significant impact on the accuracy of the Doppler BP method. These results in HeartMate 3 patients are very similar to previous results in HeartMate II and HVAD patients. Conclusions Doppler BP method should be the default non‐invasive BP measurement method in continuous flow VAD patients including patients implanted with the HeartMate 3.

Objectives The purpose of this study was to investigate the association between obtaining hemodynamic data from early pulmonary artery catheter (PAC) placement and outcomes in cardiogenic shock (CS). Background Although PACs are used to guide CS management decisions, evidence supporting their optimal use in CS is lacking. Methods The Cardiogenic Shock Working Group (CSWG) collected retrospective data in CS patients from 8 tertiary care institutions from 2016 to 2019. Patients were divided by Society for Cardiovascular Angiography and Interventions (SCAI) stages and outcomes analyzed by the PAC-use group (no PAC data, incomplete PAC data, complete PAC data) prior to initiating mechanical circulatory support (MCS). Results Of 1,414 patients with CS analyzed, 1,025 (72.5%) were male, and 494 (34.9%) presented with myocardial infarction; 758 (53.6%) were in SCAI Stage D shock, and 263 (18.6%) were in Stage C shock. Temporary MCS devices were used in 1,190 (84%) of those in advanced CS stages. PAC data were not obtained in 216 patients (18%) prior to MCS, whereas 598 patients (42%) had complete hemodynamic data. Mortality differed significantly between PAC-use groups within the overall cohort (p Conclusions The CSWG is a large multicenter registry representing real-world patients with CS in the contemporary MCS era. Use of complete PAC-derived hemodynamic data prior to MCS initiation is associated with improved survival from CS.

Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left ventricle are altered by the implantation of an LVAD, with the increase of thrombogenic flow patterns, such as stagnation regions. Time-resolved stereo particle image velocimetry (Stereo-PIV) measurements of the flow inside a patient-specific model of the left ventricle (LV) implanted with an LVAD were performed. The effects of LVAD speed, peripheral resistance and afterload were investigated. The impact of activating the LVAD pulsatility mode (periodic speed modulation) was also evaluated. Analysis of the velocity measurements in two orthogonal planes revealed stagnation zones which may be favorable to thrombus formation. Increasing LVAD speed, despite increasing the flow rate through the inflow cannula, does not automatically result in smaller stagnation regions. These results demonstrated the strong interdependence of peripheral resistance, afterload and flow through the LVAD. As a consequence, the pulsatility mode showed very limited effect on overall flow rate. However, it did reduce the size of high stagnation areas. This study showed how LVAD speed, peripheral resistance and afterload impact the complex intraventricular flow patterns in a ventricle implanted with an LVAD and quantify their thrombogenic risk.

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Mor...

Background Knowledge synthesis is lacking regarding outcomes and experiences of caregivers of adult patients living with continuous flow left ventricular assist devices (CF-LVAD). The purpose of this systematic review was to summarize qualitative data related to the experience of caregivers of adult patients living with CF-LVAD as well as quantitative data related to health outcomes of caregivers. Methods and Results Multiple databases were systematically queried for studies of qualitative experiences and quantitative health outcomes for caregivers of adult CF-LVAD recipients. Search dates were constrained to articles published between 2004 and August of 2018 because CF-LVADs were not routinely implanted before 2004. Two authors independently screened 683 articles; 15 met predetermined inclusion criteria. Eligible articles reported results from 13 studies. Of those, 8 used either qualitative or mixed methods and 5 used quantitative methods. Caregivers were primarily female (81%) and their mean age was 59 years. Qualitative studies revealed 3 overarching themes related to the caregiver role, coping strategies, and LVAD decisions. Quantitative studies revealed caregiver strain peaked between 1 and 3 months after implantation, anxiety and depression were relatively stable, mental health status improved, and physical health status was stable from before to after implantation. Conclusions CF-LVAD caregivers experience significant, sustained emotional strain for 3 months after implantation, reporting considerable stress in meeting their personal needs and those of their loved one.

Supplemental Digital Content is available in the text., This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

We discuss the ethical responsibilities of mechanical circulatory support (MCS) programs in the context of cardiac device recalls, particularly the near-simultaneous recalls of Abbott HeartMate 3 left ventricular assist device (VAD) and Medtronic HVAD devices in 2018. We consider MCS programs' ethical responsibilities toward patients who already have VADs and their caregivers, as well as the impact of recalls on informed consent and shared decision-making in patients under consideration for new VADs. Timely communication to affected patients is imperative throughout the recall process. MCS programs are required to notify existing VAD patients about the nature and likelihood of risk. A press release from the device manufacturer or other press reports may occur before MCS teams learn about the recall. This leads to a disclosure gap, where the programs are actively deciding on an appropriate action plan while simultaneously fielding patient concerns. From an ethics standpoint, if all device users are owed the recall information from the manufacturer, all patients are owed the information from their treating team. The question is what to disclose specifically, and how.

Aims Despite advances in coronary reperfusion and percutaneous mechanical circulatory support, mortality among patients presenting with cardiogenic shock (CS) remains unacceptably high. Clinical trials and risk stratification tools have largely focused on acute CS, particularly secondary to acute coronary syndrome. Considerably less is understood about CS in the setting of acute decompensation in patients with chronic heart failure (HF). We sought to compare outcomes between patients with acute CS and patients with acute on chronic decompensated HF presenting with laboratory and haemodynamic features consistent with CS. Methods and results Sequential patients admitted with CS at a single quaternary centre between January 2014 and August 2017 were identified. Acute on chronic CS was defined by having a prior diagnosis of HF. Initial haemodynamic and laboratory data were collected for analysis. The primary outcome was in‐hospital mortality. Secondary outcomes were use of temporary mechanical circulatory support, durable ventricular assist device implantation, total artificial heart implantation, or heart transplantation. Comparison of continuous variables was performed using Student's t‐test. For categorical variables, the χ 2 statistic was used. A total of 235 patients were identified: 51 patients (32.8%) had acute CS, and 184 patients (64.3%) had acute decompensation of chronic HF with no differences in age (52 ± 22 vs. 55 ± 14 years, P = 0.28) or gender (26% vs. 23%, P = 0.75) between the two groups. Patients with acute CS were more likely to suffer in‐hospital death (31.4% vs. 9.8%, P

With increasing use of left ventricular assist devices (LVAD) it is critical to devise strategies to optimize LVAD speed while controlling mean arterial pressure (MAP) and flow according to patient physiology. The complex interdependency between LVAD speed, MAP, and flow frequently makes optimization difficult under clinical conditions. We propose a method to guide this procedure in silico, narrowing the conditions to test clinically. A computational model of the circulatory network that simulates HF and LVAD support, incorporating LVAD pressure-flow curves was applied retrospectively to anonymized patient hemodynamics data from the University of Washington Medical Center. MAP management on 61 patient-specific computational models with a target of 70 mm Hg, resulting flow for a given LVAD speed was analyzed, and compared to a target output of 5 L/min. Before performing virtual MAP management, 51% had a MAP>70 mm Hg and CO>5 L/min, and 33% had a MAP>70 mm Hg and CO

Importance The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures The area under the curve (AUC) for the ratio of N-terminal pro–brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08;P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non–life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%];P = .04), there were no observed safety concerns. Conclusions and Relevance The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration ClinicalTrials.gov Identifier:NCT02816736

Objectives Management of left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH) is complicated by the competing concerns of hematoma expansion and the risk of thrombosis. Strategies include reversal or withholding of anticoagulation (AC) and neurosurgical (NSG) interventions. The consequences of these decisions can significantly impact both short- and long-term survival. Currently no guidelines exist. We reviewed medical and NSG practices following LVAD-associated ICH and analyzed outcomes. Materials and methods Retrospective analysis of data collected between 2012–2018 was performed. Survival probability following ICH was calculated using the Kaplan-Meier method. Results Out of 283 patients, 32 (11%) had 34 ICHs: 16 intraparenchymal (IPH, 47%), 4 subdural (SDH, 12%), and 14 subarachnoid (SAH, 41%). IPH tended to occur sooner (median 138 [IQR 48 – 258] days post-LVAD placement) and be more neurologically devastating (mean GCS 11.4 [4.4]). Antithrombotics were reversed in 27 (79%); 1 thrombotic event occurred while off AC. Following resumption, re-hemorrhage occurred in 7 (25%), a median of 13 days (IQR 8-30) post-ICH. Five underwent NSG intervention and 6 (18%) went on to receive heart transplant. Overall, 30-day mortality was 26% (38% in IPH, 0% in SDH, and 29% in SAH), but rose to 44% at 6 months. Conclusion ICH is a common post-LVAD complication with high short- and long-term mortality, though ICH subtypes may not be equally devastating. Despite this, some may benefit from neurosurgical intervention and do well following cardiac transplant. Anticoagulation is frequently reversed after ICH. Resumption however should be approached cautiously in patients with LVADs given their possible baseline coagulopathy.

Strokes remain a leading cause of morbidity and mortality in patients with ventricular assist devices (VADs). Varying study populations, event definitions, and reporting methods make direct comparison of neurologic event risk across clinical trials and registries challenging. We aim to highlight important differences among major VAD studies and standardize rates of neurologic events to facilitate a comprehensive and objective comparison. We systematically identified and analyzed key clinical trials and registries evaluating the HeartMate II (HMII), HeartMate 3 (HM3), and HVAD devices. Reported neurologic events were nonexclusively categorized into ischemic stroke, hemorrhagic stroke, disabling stroke, fatal stroke, and other neurologic events per the studies' definitions. Event rates were standardized to events per patient-year (EPPY) and freedom from event formats. Seven key clinical trials and registries were included in our analysis. There is significant variation and overlap in neurologic event rates for the three VAD platforms across clinical trials (all neurologic events [EPPY]: HM3 0.17-0.21; HMII 0.19-0.26; HVAD 0.16-0.28). None performs consistently better for all types of neurologic events. Furthermore, stroke rates among VAD trials correlated with baseline stroke risk factors including ischemic etiology, history of atrial fibrillation, and history of prior stroke.

Aims Accurate blood pressure (BP) measurement in continuous‐flow ventricular assist device (CF‐VAD) patients is imperative to reduce stroke risk. This study assesses the accuracy of the Doppler opening pressure method compared with the gold standard arterial line method in CF‐VAD patients. Methods and results In a longitudinal cohort of HeartMate II and HVAD patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Overall correlation, agreement between Doppler opening pressure and arterial line mean vs. systolic pressure, and the effect of arterial pulsatility on the accuracy of Doppler opening pressure were analysed. A total of 1933 pairs of Doppler opening pressure and arterial line pressure readings within 1 min of each other were identified in 154 patients (20% women, mean age 55 ± 15, 50% HeartMate II and 50% HVAD). Doppler opening pressure had good correlation with invasive mean arterial pressure (r = 0.742, P

The HeartWare centrifugal-flow ventricular assist device system (HVAD) is a viable option for treatment of advanced heart failure. There is a growing trend toward the use of less invasive techniques in cardiac surgery, and the thoracotomy technique for HVAD implantation may provide benefits not available with conventional approaches.The LATERAL trial is a multicenter, prospective, non-randomized, single-arm trial that utilized data from 144 patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database at 26 centers in the United States and Canada. The primary composite end-point was success at 180 days defined as alive on the originally implanted device and free from disabling stroke (modified Rankin Scale score3), transplanted or explanted for recovery. The key secondary end-point was mean length of initial hospital stay.The primary end-point was successfully achieved in 88.1% of patients and was significantly greater than the pre-defined performance goal of 77.5% set from historical sternotomy data (p = 0.0012). The key secondary end-point-mean length of initial hospital stay -was 18 days and was significantly shorter than the pre-defined performance goal of 26.1 days obtained from historical sternotomy data (p0.0001). The adverse event profile further demonstrated the safety of the thoracotomy approach. The overall patient survival was good, and bleeding requiring reoperation was significantly less frequent than that observed in previous studies using the sternotomy approach.This prospective clinical trial provides validation that implantation of the HVAD system via the thoracotomy approach used in the LATERAL study represents a safe and effective alternative to median sternotomy in selected patients intended for a bridge-to-transplant indication.

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63; P =0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.